Oral Mucositis (OM) is one of the most debilitating adverse effects in cancer patients treated with chemotherapy or radiation therapy. Emerging evidence suggests that the oral microbiota plays an important role in the severity of OM. In patients with cancer, a dramatic change in the oral environment occurs causing an imbalance of the oral microorganisms including bacteria, fungi, and viruses of the oral cavity. This disruption of the balance is often observed as a result of the patient's direct exposure to the cytotoxic effects of medications, alterations in cytokine release, reduced salivary flow, or use of antibiotics. Thus, the cancer treatment results in the formation of oral ulcers (i.e. oral mucositi), which are susceptible to colonization of microorganisms and disruption of the ecological balance. Currently, there are no effective therapies or preventive treatments for OM. Most suggested treatments or therapies provide minor improvements in infection rates, inflammation, irritation, or pain relief. Emerging hypotheses have speculated that oral mucositis results from the disruption of the ecological balance during cancer treatment. Several clinical studies have suggested that professional oral care could reduce the severity of OM implying that maintaining a beneficial oral microbiota may influence the course of OM by inducing changes in the oral mucosa and decreasing local inflammation. Our proposed study will investigate in a multicenter, randomized controlled clinical trial the effects of a novel oral care protocol Oral Mucosal Deterging and Periodontal Debridement (*OMDP) [27-29] on the severity of OM in patients undergoing radiation (RT) and chemoradiation (chemoRT) for head and neck cancer. Additionally, it will evaluate the effect of RT/chemoRT on the oral microbiome and its impact on OM severity and local inflammation. Other clinical indicators of the intervention (i.e. OM pain, salivary flow rates and quality of life) will also be evaluated before, during and after RT. The central hypothesis is that a bi-weekly regimen of targeted professional oral hygiene during cancer treatment prevents harmful ecological shifts in the oral cavity and consequently reduces the duration and severity of OM, decreases inflammation and OM pain, and improves oral health, thereby improving overall quality of life during cancer treatment. The rationale is that th mechanical removal of dead, damaged, or infected oral mucosa tissues in combination with removal of dental plaque and calculus in the oral cavity during RT/chemoRT treatment improves the healing potential of the oral tissues and suppresses OM severity. [*The OMDP protocol consists of a regimen of frequent professional oral prophylaxis during cancer treatment; including tooth cleaning, tooth polishing and flossing, the deterging of the oral mucosa and periodontal debridement. Mucosal Deterging: wipe or wash away/to cleanse of impurities or undesirable matter, as a wound. Periodontal Debridement: mechanical removal of supra-and subgingival plaque and calculus from tooth surfaces]